Giant viruses challenge traditional boundaries of virology with their large particle sizes, complex genomes, and unique replication strategies. Yet, despite its 750 nm diameter and incorporation of dozens of distinct proteins, the mimivirus virion retains an icosahedral symmetry, often associated with smaller spherical viruses. The functional roles and interactions of most of the proteins in such complex icosahedral particles remain elusive. Here, we employed endogenous tagging combined with co-immunoprecipitation coupled to mass spectrometry to reveal distinct interaction modules associated with the virion membrane, nucleoid and viral factory.